ESTRO 37 Abstract book

S141

ESTRO 37

Material and Methods The NAR score was available in 1191 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. The NAR score was classified as low (NAR<8), intermediate (NAR=8-16), and high (NAR>16) according to the NSABP R-04 trial dataset that demonstrated better overall survival rates with lower NAR. Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. Results After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT significantly improved 3-year DFS (75.9% [95% CI 72.30-79.50] vs 71.3% [95% CI 67.60-74.90]; p=0.034; PC 1) and resulted in a shift towards lower NAR groups (p=0.034, PC 2) compared to fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI, 88.2-95.2), 81.8% (95% CI, 78.4-85.1) and 58.1 (95% CI 52.4-63.9) for low, intermediate and high NAR score, respectively (p<0.001; PC 3). NAR score remained an independent prognostic factor for DFS (low vs high NAR: HR 4.670; 95% CI 3.106-7.020; p<0.001; low vs intermediate NAR: HR 1.971; 95% CI 1.303-2.98; p=0.001) in multivariable analysis. The treatment effect on DFS was captured by NAR (HR = 2.34; 95% CI, 1.125-4.866; p=0.023), satisfying individual-level PC 4. Conclusion This is, to our knowledge, the first study to validate the prognostic role and surrogacy of NAR score for DFS within a large randomized phase 3 trial based on the strict Prentice criteria. Our results corroborate the National Research Group (NRG) Oncology and the National Cancer Institute (NCI) Clinical Trials Network strategy to use NAR score as the primary endpoint in early phase trials. The NAR score constitutes an immediately available and easily usable endpoint that can predict treatment effects on the clinical outcome and help to speed up response- adapted therapeutic decisions. Further large phase 3 trial datasets are required to confirm trial-level surrogacy. OC-0279 a randomized phase II study testing for optimal strategy for patients with high risks rectal cancer T. Vuong 1 , P. Kavan 2 , A.G. Martin 3 , L. Azoulay 4 , D. Donath 5 , C. Lavoie 6 , E. Ferland 7 , N. Nguyen 8 , C.A. Vasilevsky 9 , S. Desgroseilliers 10 , S. Drolet 11 , C. Richard 12 , M. Boutros 13 , G. Batist 14 1 Jewish General Hospital- McGill University, Radiation Oncology Department oncology, Montreal, Canada 2 Jewish General Hospital-McGill University, Medical Oncology Department oncology, Montreal, Canada 3 University of Laval- Quebec, Radiation Oncology, Quebec, Canada 4 Jewish General Hospital. McGill University, Epidemiology and Statistics- Department oncology, Montreal, Canada 5 CHUM- University of Montreal-, Radiation Oncology, Montreal, Canada 6 CHUQ- university of Laval, Radiation Oncology, Quebec, Canada 7 Pierre Boucher Hospital, Medical Oncology, Longueil- Quebec, Canada 8 Charles Lemoyne Hospital, Medical Oncology, Longueil, Canada 9 Jewish General Hospital- McGill University, Colo-rectal surgery Department oncology, Montreal, Canada 10 Pierre Boucher Hospital, General Surgery, Longueil- Quebec, Canada 11 CHUQ- university of Laval, Colo-rectal surgery, Quebec, Canada 12 CHUM- University of Montreal-, Colo-rectal surgery, Montreal, Canada 13 Jewish General Hospital- McGill University, Colo-rectal

surgery, Montreal, Canada 14 Jewish General Hospital- McGill University, Medical Oncology Department oncology, Montreal, Canada Purpose or Objective In North America, the standard of care for locally advanced rectal cancer is neoadjuvant chemo-radiation therapy (CRT) prior to total mesorectal surgery (TME) followed by adjuvant chemotherapy (CT). This results in a median time of 4.5-5.5 months from the start of local therapy to the start of systemic treatment.The present study is proposing to evaluate a modified strategy to shorten the local disease treatment time to 2.5-3.5 months with targeted high dose rectal brachytherapy (HDRBT) to allow for optimization of systemic therapy with FOLFOX CT given either in neoadjuvant or adjuvant setting. Material and Methods The primary endpoint is patient compliance to CT. A total of 180 patients were randomized using a 2:1 ratio to arm A: Pre-operative six cycles of FOLFOX CT followed by Imaged guided HDRBT to deliver 26 Gy in 4 fractions, then TME and 6 cycles of adjuvant CT; or arm B. Pre- operative HDRBT, TME and 12 cycles of adjuvant FOLFOX CT. The primary outcome was compliance rate to the first 6 cycles of CT.This study was approved by the Institutional Review Board of each of the five participating centers and written informed consent was obtained for eligible pts. Results 180 pts without metastases were recruited with 120 pts treated in arm A (neoadjuvant FOLFOX) and 60 patients in arm B (adjuvant FOLFOX). The CT compliance rate of 78.1 % for arm A compared to 51.9% in arm B P =.(p = 0.0008)..Grade 3 & 4 toxicity rate during chemotherapy was simllar with 29% for arm A and 31% for arm B. One patient in arm A died during CT (Grade 5). HDREBT was feasible in all patients but 4 pts. One patient refused HDRBT after randomization (arm B) and 3 patients on arm A had local tumor progression and were not deemed for HDRBT and all received a short course of external beam radiation therapy. Two patients refused surgery after neoadjuvant treatment. On an intention to treat basis, the pT0 rate was 35.2% for arm A and 32.1 % for arm B while the pT0N0 rate was respectively 28.7% and 22.4% (p= 0.72073). With a median follow up of 37 months (range: 11-84), the secondary outcomes for arms A and B at 3 years were respectively, local recurrence rate was 3% and 5% (p=0.9893), Disease free survival 80 % and 76%, (p=0.6020), the cancer specific survival was 94% and 92% (p=0.8386) and overall survival rate 94% and 85% The safety and improved compliance to neoadjuvant CT is confirmed in this multi-institutional randomized phase II study using HDREBT as a neoadjuvant RT modality for rectal cancer.The good oncological outcomes obtained in this patient population at the time of this reporting are encouraging. . OC-0280 Proctitis after brachytherapy for rectal cancer: clinical and dosimetric factors - The HERBERT study E.C. Rijkmans 1 , R.A. Nout 1 , E.M. Kerkhof 1 , A. Cats 2 , B. Van Triest 3 , A. Inderson 4 , R.P.J. Van den Ende 1 , M.S. Laman 1 , M. Ketelaars 1 , C.A.M. Marijnen 1 1 Leiden University Medical Center LUMC, Department of Radiotherapy, Leiden, The Netherlands 2 The Netherlands Cancer Institute, Department of Gastroenterology, Amsterdam, The Netherlands 3 The Netherlands Cancer Institute, Department of Radiotherapy, Amsterdam, The Netherlands 4 Leiden University Medical Center LUMC, Department of Gastroenterology, Leiden, The Netherlands (p=0.5327). Conclusion